M-J Ma1, X-X Wang2, M-N Wu3, X-J Wang4, C-J Bao5, H-J Zhang6, Y Yang7, K Xu5, G-L Wang8, M Zhao9, W Cheng2, W-J Chen3, W-H Zhang8, L-Q Fang8, W J Liu10, E-F Chen11, W-C Cao8. 1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: mjma@163.com. 2. Department of Acute Infectious Disease Control and Prevention, Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China. 3. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Department of Acute Infectious Disease Control and Prevention, Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China. 4. Department of Acute Infectious Disease Control and Prevention, Shandong Provincial Centre for Disease Control and Prevention, Jinan, China. 5. Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Centre for Disease Control and Prevention, Nanjing, China. 6. National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China. 7. Department of Biostatistics, University of Florida, Gainesville, FL, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA. 8. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. 9. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. 10. National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China. Electronic address: liujun@ivdc.chinacdc.cn. 11. Department of Acute Infectious Disease Control and Prevention, Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, China. Electronic address: enfchen@cdc.zj.cn.
Abstract
OBJECTIVES: Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. METHODS: A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. RESULTS: A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17-6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08-2.63), underlying medical conditions (1.94, 95% CI 1.09-3.46) and lack of antiviral therapy (2.08, 95% CI 1.04-4.17) were predictors for higher T-cell responses. CONCLUSIONS: Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.
OBJECTIVES: Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. METHODS: A cross-sectional study was conducted to investigate the immune memory responses of H7N9patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. RESULTS: A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17-6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08-2.63), underlying medical conditions (1.94, 95% CI 1.09-3.46) and lack of antiviral therapy (2.08, 95% CI 1.04-4.17) were predictors for higher T-cell responses. CONCLUSIONS: Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.
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